Abstract

BackgroundWall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atherosclerotic mouse model. To determine WSS in vivo, detailed 3D geometry of the vessel network is required. However, a protocol to reconstruct 3D murine vasculature using this animal model is lacking. In this project, we evaluated the adequacy of eXIA 160, a small animal contrast agent, for assessing murine vascular network on micro-CT. Also, a protocol was established for vessel geometry segmentation and WSS analysis.MethodsA tapering cast was placed around the right common carotid artery (RCCA) of ApoE−/− mice (n = 8). Contrast-enhanced micro-CT was performed using eXIA 160. An innovative local threshold-based segmentation procedure was implemented to reconstruct 3D geometry of the RCCA. The reconstructed RCCA was compared to the vessel geometry using a global threshold-based segmentation method. Computational fluid dynamics was applied to compute the velocity field and WSS distribution along the RCCA.ResultseXIA 160-enhanced micro-CT allowed clear visualization and assessment of the RCCA in all eight animals. No adverse biological effects were observed from the use of eXIA 160. Segmentation using local threshold values generated more accurate RCCA geometry than the global threshold-based approach. Mouse-specific velocity data and the RCCA geometry generated 3D WSS maps with high resolution, enabling quantitative analysis of WSS. In all animals, we observed low WSS upstream of the cast. Downstream of the cast, asymmetric WSS patterns were revealed with variation in size and location between animals.ConclusionseXIA 160 provided good contrast to reconstruct 3D vessel geometry and determine WSS patterns in the RCCA of the atherosclerotic mouse model. We established a novel local threshold-based segmentation protocol for RCCA reconstruction and WSS computation. The observed differences between animals indicate the necessity to use mouse-specific data for WSS analysis. For our future work, our protocol makes it possible to study in vivo WSS longitudinally over a growing plaque.

Highlights

  • Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis

  • Atherosclerotic plaques are predisposed to develop at the inner curvatures and branches of the arterial system, a process which is known to be driven by the local wall shear stress (WSS) environment [3, 4]

  • The aim of this study was to determine whether eXIA 160 is a suitable contrast agent for reconstructing reliable 3D geometry for computational fluid dynamics (CFD) analyses in the WSS-manipulated atherosclerotic mouse model

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Summary

Introduction

Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atherosclerotic mouse model. Atherosclerotic plaques are predisposed to develop at the inner curvatures and branches of the arterial system, a process which is known to be driven by the local wall shear stress (WSS) environment [3, 4]. The pro-inflammatory status of the endothelial cells primes the vessel wall for atherosclerotic development [3]. In order to study the effect of different WSS patterns on plaque progression in vivo, a WSS-induced atherosclerotic mouse model has been developed [8]. In this model, a tapering cast is placed around the animal’s right common carotid artery (RCCA), inducing distinct WSS patterns in this vessel. There were less than 5% differences between the two segmented vessels, indicating that the vessel reconstruction was not influenced by the segmentation method

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